Objectives of this project are (1) to establish and define a cell culture transformation system for identification of carcinogenic agents and humans at high risk for cancer; and (2) to develop human cell transformation systems, with particular emphasis on epithelial cells. In order to study host factors regulating cell transformation and the mechanisms of carcinogenesis by chemicals, hormones and x-irradiation; and (3) to study roles of activated and suppressor oncogenes in neoplastic transformation. We have demonstrated (1) neoplastic transformation of immortalized human epidermal keratinocytes by exposure to x-ray irradiation; (2) morphological transformation of human keratinocytes expressing the latent membrane protein (LMP) gene of Epstein-Barr virus: (3) demonstration of CR-2, a cell surface membrane glycoprotein in an immortalized human epidermal keratinocyte line; and (4) establishment of a cystic fibrosis bronchial epithelial cell line by adenovirus 12-SV40 (Adl2-SV40) virus infection.